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Gastric/GEJ Cancers: Looking Toward the Future

Insights From: Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Alan P. Venook, MD, University of California San Francisco; Zev A. Wainberg, MD, UCLA School of Medicine
Published: Thursday, Feb 08, 2018



Transcript: 

Zev A. Wainberg, MD: In gastric and gastroesophageal junction cancers, there’s actually a lot of interest and energy now. There are a lot of new clinical trials, new drug developments, being pursued in these 2 cancers that are often bunched together. I think that immunotherapy obviously now has a role, and that’s been one of the bright spots in GI cancer, in my opinion. That has been its role in gastric cancer. So, that’s leading the way in many ways for all of the new drug developments.

Beyond that, there are a number of new targeted therapies that look promising, such as claudin inhibitors, second-generation HER2 inhibitors, VEGFR inhibitors that may be used now beyond the salvage setting, and targets that nobody even knows much about. We have drug development going on in gastric cancer, such as with matrix metalloproteinase inhibitors and a whole host of other drugs that are out there, which are looking interesting and exciting. In many ways, we’re hoping in the next few years gastric cancer will start to be further subclassified based on the predictive biomarkers of drugs. We’ll hopefully be treating this cancer in the next few years very differently than we are today.

Alan P. Venook, MD: The most exciting thing about GE junction and gastric cancers has certainly been the evolution of checkpoint inhibitors and the Tumor Cancer Genome Atlas, which gives us a handle on a lot of the molecular features that may be worth targeting. It’s a different question of whether we can intervene early enough and make a big enough difference in patients, because a disease is typically advanced by the time we find it. It has so many consequences in the body: the malnourishment, the general sense of ill-being, and the frequently abdominal metastases that affect the function of the bowel.

Those make it a very hard disease to treat, and I worry that treating advanced disease will never get very far along. The key would be finding the disease earlier, if we could. In Asia, they find it early because they screen for the disease. It’s that common. In the West, we don’t do that, and I believe it will forever be a great challenge in these patients because they’re so sick for the relative amount of cancer that they have.

Yelena Y. Janjigian, MD: Gastric cancer is an orphan disease. In United States, we have 20,000 cases each year. Compared to metastatic lung cancer, breast cancer, or colon cancer, there are 200,000 cases. So, it’s a rare disease. Historically, to lead the innovation and ideas and drug development, it’s really important to try to treat these patients in the setting of a clinical trial. If you don’t observe these patients in a setting where it’s a fixed environment where you can learn a lot from their tumor or biologic behavior, the next generation of trials and hypotheses cannot be formatted.

Regarding the enrollment in these clinical trials, particularly for HER2 or immunotherapy-directed studies, we have a lot of ideas and a lot of clinical trials, but not enough patients going on them. Most of the time, what happens is that because gastric cancer is so common in Asia, these global studies are flooded by the Asian population. The biology of the tumor is quite distinct, or can be quite distinct, and therefore, it does not help us answer our questions that are important for our patients in the United States. We have to do the work ourselves and motivate our patients and our practitioners to refer patients for clinical trials, because that’s the only way that we can advance the field.

Transcript Edited for Clarity 
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Transcript: 

Zev A. Wainberg, MD: In gastric and gastroesophageal junction cancers, there’s actually a lot of interest and energy now. There are a lot of new clinical trials, new drug developments, being pursued in these 2 cancers that are often bunched together. I think that immunotherapy obviously now has a role, and that’s been one of the bright spots in GI cancer, in my opinion. That has been its role in gastric cancer. So, that’s leading the way in many ways for all of the new drug developments.

Beyond that, there are a number of new targeted therapies that look promising, such as claudin inhibitors, second-generation HER2 inhibitors, VEGFR inhibitors that may be used now beyond the salvage setting, and targets that nobody even knows much about. We have drug development going on in gastric cancer, such as with matrix metalloproteinase inhibitors and a whole host of other drugs that are out there, which are looking interesting and exciting. In many ways, we’re hoping in the next few years gastric cancer will start to be further subclassified based on the predictive biomarkers of drugs. We’ll hopefully be treating this cancer in the next few years very differently than we are today.

Alan P. Venook, MD: The most exciting thing about GE junction and gastric cancers has certainly been the evolution of checkpoint inhibitors and the Tumor Cancer Genome Atlas, which gives us a handle on a lot of the molecular features that may be worth targeting. It’s a different question of whether we can intervene early enough and make a big enough difference in patients, because a disease is typically advanced by the time we find it. It has so many consequences in the body: the malnourishment, the general sense of ill-being, and the frequently abdominal metastases that affect the function of the bowel.

Those make it a very hard disease to treat, and I worry that treating advanced disease will never get very far along. The key would be finding the disease earlier, if we could. In Asia, they find it early because they screen for the disease. It’s that common. In the West, we don’t do that, and I believe it will forever be a great challenge in these patients because they’re so sick for the relative amount of cancer that they have.

Yelena Y. Janjigian, MD: Gastric cancer is an orphan disease. In United States, we have 20,000 cases each year. Compared to metastatic lung cancer, breast cancer, or colon cancer, there are 200,000 cases. So, it’s a rare disease. Historically, to lead the innovation and ideas and drug development, it’s really important to try to treat these patients in the setting of a clinical trial. If you don’t observe these patients in a setting where it’s a fixed environment where you can learn a lot from their tumor or biologic behavior, the next generation of trials and hypotheses cannot be formatted.

Regarding the enrollment in these clinical trials, particularly for HER2 or immunotherapy-directed studies, we have a lot of ideas and a lot of clinical trials, but not enough patients going on them. Most of the time, what happens is that because gastric cancer is so common in Asia, these global studies are flooded by the Asian population. The biology of the tumor is quite distinct, or can be quite distinct, and therefore, it does not help us answer our questions that are important for our patients in the United States. We have to do the work ourselves and motivate our patients and our practitioners to refer patients for clinical trials, because that’s the only way that we can advance the field.

Transcript Edited for Clarity 
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